Introduction The neuropsychological deterioration after cardiac surgery involving cardiopulmonary bypass (CPB), is ascribed to brain ischaemia caused by, amongst others, hypotension, cerebral hyperthermia, cerebral embolism, interaction between pharmacological methods and hypothermia during ischaemia, and the directly neurotoxic of anaesthetic drugs. AimTo investigate the effect of the anaesthetic techniques midazolam plus ketamine (MK) or sufentanil (S) on the quantitative EEG (QEEG), reaction time (RT), serum neuron specific enolase (NSE), and serum S-100<font face="symbol">b</font> protein after cardiac surgery involving CPB in humans. Patients and methodsThe sample consisted of a total of 42 patients scheduled for elective coronary artery bypass (CABG) or valve replacement (VR). All patients were not available for all the postoperative tests. Patients were allocated randomly to group MK or S. Anaesthetic technique: S or MK. Isoflurane was administered when necessary. CPB technique: 30°C, membrane oxygenation, a 40 <font face="symbol">m</font>m filter in the arterial cannula and <font face="symbol">a</font>-stat-blood gas management, blood pressure of 50 to 70 mm Hg and a haematocrit <font face="symbol">></font> 22%. Patients were weaned from CPB when nasopharyngeal temperature reached a maximum of 37,5°C. QEEG and RT was performed 1 to 2 days preoperatively and 5 to 6 days postoperatively.Serum-NSE and -S-100<font face="symbol">b</font> protein were measured preoperatively, 2 minutes after going on CPB, after rewarming to 37°C, just before the end of CPB and 2, 4, 10, 20, 30, and 48 hours after CPB. ResultsQEEG: The most noticable finding was an increase in slow wave activity (relative <font face="symbol">q</font> and <font face="symbol">s</font>). The QEEG outcome was better after CABG than after VR (p < 0,001), but not different between MK and S (p = 0,5000). <font face="symbol">Dq</font>% was better with MK than S (p = 0,0120). <font face="symbol">Dq</font>% (p = 0,0010), <font face="symbol">Da/q</font>% (p = 0,0090) and <font face="symbol">D</font>PS% (p = 0,0025) was better after CABG than VR. Reaction time: There was a significant deterioration in 5/18 (27,78%) of MK and 12/18 (66,67%) of S (p = 0,0220). The change in accuracy in sequential reation time 1 (p = 0,0100), and sequential reation time 2 (p = 0,0970) and the cumulative accuracy was better with MK than S(p = 0,0020). Chemical markers: Over groups 14,8% of patients had a poor NSE and 61,9% a poor S-100<font face="symbol">b</font> outcome. Within groups a poor NSE outcome was found in 14,8% of MK and 14,8% of S (p = 1,0000), and 4,8% of CABG but 23,8% of VR (p = 0,1840). Within groups as adverse S-100<font face="symbol">b</font> outcome was found in 42,9% of MK but 81,0% van S (p = 0,0250; Fisher's exact test), and 66,7% of CABG and 57,1% of KV (p = 0,7510. According to area under the curve of corrected NSE, CABG had a better outcome than VR (p = 0,0040). According to both maximum S-100<font face="symbol">b</font> level and the area under the curve of S-100<font face="symbol">b</font>, an interaction occurred between the anaesthetic technique and the procedure, with VR doing better with MK while CABG did significantly better with S (p = 0,0180 en 0,0040 respectively). Conclusion, shortcomings, significance and contribution This study has shown that, in as far as brain damage is concerned, the outcome was probably better with MK than with S, and CABG better than VR. An interaction was found between the anaesthetic technique and the type of operation.